Clinical Information
Gen. Code and Des.
7858 levobunolol HCl OPHTHALMIC DROPS 0.5 %
GCN and Des.
33310 levobunolol HCl OPHTHALMIC DROPS 0.5 %
Strength
0.5%
Dose Form
DROPS
Product Category
RX Pharmaceuticals
Fine Line Class
850085008510 All Rx Products
DEA Class
NC
OMP Family
AHFS Class
52400800 BETA-ADRENERGIC BLOCKING AGENTS (EENT)
Active Ingredients
1860 levobunolol HCl 27912147
Inactive Ingredients
3141 benzalkonium chloride 8001545
3785 edetic acid 60004
6300 sulfite 14265453
LEVOBUNOLOL HYDROCHLORIDE- levobunolol hydrochloride solution/ drops
Pacific Pharma, Inc.
DESCRIPTION
Levobunolol HCl ophthalmic solution, USP is a noncardioselective beta-adrenoceptor blocking agent for ophthalmic use. The solution is colorless to slightly light yellow in appearance with an osmolality range of 250-360 mOsm/kg. The shelf life pH range is 5.5 to 7.5.
Chemical Name: (-)-(S)-5-[3-(tert -Butylamino)-2-hydroxypropoxy]-3,4-dihydro-1(2H)-naphthalenone hydrochloride.
Structural Formula: levobunolol HCl
Chemical Structure
(click image for full-size original)
Contains: Active: Levobunolol HCl 0.25% or 0.5%. Preservative: benzalkonium chloride 0.004%. Inactives: edetate disodium; polyvinyl alcohol 1.4%; potassium phosphate, monobasic; purified water; sodium chloride; sodium metabisulfite; sodium phosphate, dibasic; and hydrochloric acid or sodium hydroxide to adjust pH.
CLINICAL PHARMACOLOGY
Levobunolol HCl is a noncardioselective beta-adrenoceptor blocking agent, equipotent at both beta1 and beta2 receptors. Levobunolol HCl is greater than 60 times more potent than its dextro isomer in its beta-blocking activity, yet equipotent in its potential for direct myocardial depression. Accordingly, the levo isomer, levobunolol HCl, is used. Levobunolol HCl does not have significant local anesthetic (membrane-stabilizing) or intrinsic sympathomimetic activity.
Beta-adrenergic receptor blockade reduces cardiac output in both healthy subjects and patients with heart disease. In patients with severe impairment of myocardial function, beta-adrenergic receptor blockade may inhibit the stimulatory effect of the sympathetic nervous system necessary to maintain adequate cardiac function.
Beta-adrenergic receptor blockade in the bronchi and bronchioles results in increased airway resistance from unopposed parasympathetic activity. Such an effect in patients with asthma or other bronchospastic conditions is potentially dangerous.
Levobunolol HCl ophthalmic solution, USP has been shown to be an active agent in lowering elevated as well as normal intraocular pressure (IOP) whether or not accompanied by glaucoma. Elevated IOP presents a major risk factor in glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss.
The onset of action with one drop of levobunolol HCl can be detected within one hour after treatment, with maximum effect seen between 2 and 6 hours.
A significant decrease in IOP can be maintained for up to 24 hours following a single dose.
In two, separate, controlled studies (one three month and one up to 12 months duration) levobunolol HCl ophthalmic solution 0.25% b.i.d. controlled the IOP of approximately 64% and 70% of the subjects. The overall mean decrease from baseline was 5.4 mm Hg and 5.1 mm Hg respectively. In an open-label study, levobunolol HCl ophthalmic solution 0.25% q.d. controlled the IOP of 72% of the subjects while achieving an overall mean decrease of 5.9 mm Hg.
In controlled clinical studies of approximately two years duration, intraocular pressure was well-controlled in approximately 80% of subjects treated with levobunolol HCl ophthalmic solution 0.5% b.i.d. The mean IOP decrease from baseline was between 6.87 mm Hg and 7.81 mm Hg. No significant effects on pupil size, tear production or corneal sensitivity were observed. Levobunolol HCl ophthalmic solution at the concentrations tested, when applied topically, decreased heart rate and blood pressure in some patients. The IOP-lowering effect of levobunolol HCl was well maintained over the course of these studies.
In a three month clinical study, a single daily application of levobunolol HCl ophthalmic solution 0.5% controlled the IOP of 72% of subjects achieving an overall mean decrease in IOP of 7.0 mm Hg.
The primary mechanism of the ocular hypotensive action of levobunolol HCl in reducing IOP is most likely a decrease in aqueous humor production. Levobunolol HCl reduces IOP with little or no effect on pupil size or accommodation in contrast to the miosis which cholinergic agents are known to produce. The blurred vision and night blindness often associated with miotics would not be expected and have not been reported with the use of levobunolol HCl ophthalmic solution. This is particularly important in cataract patients with central lens opacities who would experience decreased visual acuity with pupillary constriction.
INDICATIONS AND USAGE
Levobunolol HCl ophthalmic solution has been shown to be effective in lowering intraocular pressure and may be used in patients with chronic open-angle glaucoma or ocular hypertension.